Splicing potentiation by growth factor signals via estrogen receptor phosphorylation

Mitogen-activated protein kinase-mediated growth factor signals are known to augment the ligand-induced transactivation function of nuclear estrogen receptor α (ERα) through phosphorylation of Ser-118 within the ERα N-terminal transactivation (activation function-1) domain. We identified the spliceosome component splicing factor (SF)3a p120 as a coactivator specific for human ERα (hERα) activation function-1 that physically associated with ERα dependent on the phosphorylation state of Ser-118. SF3a p120 potentiated hERα-mediated RNA splicing, and notably, the potentiation of RNA splicing by SF3a p120 depended on hER Ser-118 phosphorylation. Thus, our findings suggest a mechanism by which growth factor signaling can regulate gene expression through the modulation of RNA splicing efficiency via phosphorylation of sequence-specific activators, after association between such activators and the spliceosome.